The overall goals of the Early Detection Research Network (EDRN) are to: a) identify biomarkers for cancer risk, early detection, molecular diagnostics, and prognosis of early cancer; and b) coordinate biomarker research and therapeutic strategies in order to reduce cancer morbidity and mortality. As a Clinical Validation Center (CVC), Fox Chase Cancer Center (FCCC) will: 1) maintain the FCCC multidisciplinary team of biomarker validation investigators; 2) comply with terms and conditions of the EDRN cooperative agreement including data sharing; 3) partner with EDRN Biomarker Development Labs (BDLs), Biomarker Reference Labs (BRLs), CVCs, and the Data Management and Coordination Center (DMCC); 4) participate in EDRN Steering Committee and Scientific meetings and activities and the EDRN Breast/Ovarian Cancer Consortium Group; 5) collect, store and distribute tissue, sera, and DNA for biomarker discovery and validation research especially from women at risk for breast and ovarian cancer; 6) partner with Geisinger Medical Center to develop population-based biomarker research validation studies. FCCC-EDRN-CVC proposes an investigator-initiated proteomic and DNA methylation phase II biomarker validation research project in women with benign breast disease (BBD) who are at risk for invasive cancer. This research utilizes biosamples collected during the past five years of EDRN funding. The aims are as follows: Study 1, Validation of candidate proteomic biomarker in BBD. Aim 1, verify that protein biomarker can distinguish preca-ncer lesions; Aim 2, validate proteomic biomarker in a set of well annotated clinical specimens. Study 2 Validations of Hypermethylated Markers. Aim 1, verify gene methylation for risk stratification in BBD; Aim 2, develop a serum-based assay in women with BBD. Numerous collaborators in and outside EDRN will utilize the FCCC-EDRN-CVC large annotated collection of breast and ovarian benign and cancer sera, DNA, and tissue samples. The proposed validation study is focused on BBD and investigates protein and DNA methylation in the same cases. The FCCC EDRN-CVC will help to translate biomarker research to community practice.